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Differences between two strains of myelin basic protein (MBP) TCR transgenic mice: implications for tolerance
Fei Song1, Richard M Wardrop, Ingrid E Gienapp
1Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University College of Medicine and Public Health, Columbus 43210, USA.
Journal of Autoimmunity
|March 1, 2002
Summary
Oral administration of myelin basic protein (MBP) protects mice from experimental autoimmune encephalomyelitis (EAE). Differences in T cell environments within the gut-associated lymphoid tissue (GALT) influence oral tolerance induction.
Area of Science:
- Immunology
- Neuroscience
- Gastroenterology
Background:
- Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated autoimmune disease.
- Myelin basic protein (MBP) is a key antigen in EAE, and T cell receptor (TCR) usage, specifically Vbeta8.2, is preferential.
- Oral administration of MBP can induce tolerance and protect against EAE, but the mechanisms vary between different transgenic mouse strains.
Purpose of the Study:
- To investigate the differences in peripheral and gut-associated lymphoid tissue (GALT) environments between two transgenic mouse strains (Valpha2.3/Vbeta8.2 and Valpha4/Vbeta8.2) with distinct TCRs recognizing an MBP epitope.
- To elucidate how these microenvironmental differences influence oral tolerance induction.
Main Methods:
- Analysis of peripheral and GALT (specifically Peyer's patch and spleen) immune cell populations in Valpha2.3/Vbeta8.2 and Valpha4/Vbeta8.2 transgenic mice.
- Assessment of immune cell markers (CD69, CD45RB), cytokine profiles (Th1, Th2), proliferative activity, and chemokine expression (MCP-1).
Main Results:
- Transgenic (Tg) T cells in the Peyer's patch (PP) of Valpha2.3/Vbeta8.2 mice showed increased CD69 and decreased CD45RB compared to Valpha4/Vbeta8.2 mice.
- Higher levels of Th1/Th2 cytokines, proliferation, and CC chemokines (MCP-1) were detected in the periphery and GALT of Valpha2.3/Vbeta8.2 Tg mice.
- Conversely, Valpha4/Vbeta8.2 mice exhibited a greater presence of non-Tg CD4+ cells in the PP.
Conclusions:
- Activated Tg T cells and a reduced number of potential regulatory cells in the PP of Valpha2.3/Vbeta8.2 Tg mice may contribute to altered oral tolerance.
- The distinct immune microenvironments within the GALT play a critical role in modulating the efficacy of oral tolerance induction for autoimmune diseases like EAE.